PDBsum entry 4wvm

Toxin

PDB id: 4wvm

Contents

Protein chains

612 a.a.

616 a.a.

PDB id:

4wvm

Name:

Toxin

Title:

Stonustoxin structure

Structure:

Stonustoxin subunit alpha. Chain: a. Synonym: sntx subunit alpha. Stonustoxin subunit beta. Chain: b. Synonym: sntx subunit beta

Source:

Synanceia horrida. Estuarine stonefish. Organism_taxid: 13279. Organism_taxid: 13279

Resolution:

3.10Å R-factor: 0.209 R-free: 0.236

Authors:

A.M.Ellisdon,S.Panjikar,J.C.Whisstock,S.Mcgowan

Key ref:

A.M.Ellisdon et al. (2015). Stonefish toxin defines an ancient branch of the perforin-like superfamily. Proc Natl Acad Sci U S A, 112, 15360-15365. PubMed id: 26627714 DOI: 10.1073/pnas.1507622112

Date:

06-Nov-14 Release date: 02-Dec-15

Protein chain

Q98989  (STXA_SYNHO) -  Stonustoxin subunit alpha from Synanceia horrida

Seq: 703 a.a.

Struc: 612 a.a.

Protein chain

Q91453  (STXB_SYNHO) -  Stonustoxin subunit beta from Synanceia horrida

Seq: 700 a.a.

Struc: 616 a.a.

DOI no: 10.1073/pnas.1507622112

Proc Natl Acad Sci U S A 112:15360-15365 (2015)

PubMed id: 26627714

Stonefish toxin defines an ancient branch of the perforin-like superfamily.

A.M.Ellisdon, C.F.Reboul, S.Panjikar, K.Huynh, C.A.Oellig, K.L.Winter, M.A.Dunstone, W.C.Hodgson, J.Seymour, P.K.Dearden, R.K.Tweten, J.C.Whisstock, S.McGowan.

ABSTRACT

The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and β), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom.